| First Author | Sommer D | Year | 2019 |
| Journal | Brain Behav Immun | Volume | 80 |
| Pages | 129-145 | PubMed ID | 30851378 |
| Mgi Jnum | J:291554 | Mgi Id | MGI:6444928 |
| Doi | 10.1016/j.bbi.2019.02.032 | Citation | Sommer D, et al. (2019) ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury. Brain Behav Immun 80:129-145 |
| abstractText | A disintegrin and metalloproteinase 17 (ADAM17) is the major sheddase involved in the cleavage of a plethora of cytokines, cytokine receptors and growth factors, thereby playing a substantial role in inflammatory and regenerative processes after central nervous system trauma. By making use of a hypomorphic ADAM17 knockin mouse model as well as pharmacological ADAM10/ADAM17 inhibitors, we showed that ADAM17-deficiency or inhibition significantly increases clearance of apoptotic cells, promotes axon growth and improves functional recovery after spinal cord injury (SCI) in mice. Microglia-specific ADAM17-knockout (ADAM17flox(+/+)-Cx3Cr1 Cre(+/-)) mice also showed improved functional recovery similar to hypomorphic ADAM17 mice. In contrast, endothelial-specific (ADAM17flox(+/+)-Cdh5Pacs Cre(+/-)) and macrophage-specific (ADAM17flox(+/+)-LysM Cre(+/-)) ADAM17-knockout mice or bone marrow chimera with transplanted ADAM17-deficient macrophages, displayed no functional improvement compared to wild type mice. These data indicate that ADAM17 expression on microglia cells (and not on macrophages or endothelial cells) plays a detrimental role in inflammation and functional recovery after SCI. |
